Physicochemical Properties
| Molecular Formula | C20H17F2N3O3 |
| Molecular Weight | 385.3641 |
| Exact Mass | 385.123 |
| CAS # | 1464842-09-8 |
| PubChem CID | 89855776 |
| Appearance | Off-white to light yellow solid powder |
| LogP | 2.5 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 28 |
| Complexity | 612 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | FC1C([H])=C(C([H])=C(C=1[H])C([H])([H])N([H])C([C@@]1(C(N(C2C([H])=C([H])C3=C(C([H])=C([H])N3[H])C=2[H])C([H])([H])C1([H])[H])=O)O[H])=O)F |
| InChi Key | WVGGJQVCOTYFPV-FQEVSTJZSA-N |
| InChi Code | InChI=1S/C20H17F2N3O3/c21-14-7-12(8-15(22)10-14)11-24-18(26)20(28)4-6-25(19(20)27)16-1-2-17-13(9-16)3-5-23-17/h1-3,5,7-10,23,28H,4,6,11H2,(H,24,26)/t20-/m0/s1 |
| Chemical Name | (3S)-N-[(3,5-difluorophenyl)methyl]-3-hydroxy-1-(1H-indol-5-yl)-2-oxopyrrolidine-3-carboxamide |
| Synonyms | M8891; M-8891 |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | The IC50 of M8891 for HUVEC proliferation is 20 nM [1]. |
| ln Vivo | M8891 has potent anti-tumor growth effects when taken orally at a dose of 20 mg/kg once daily for 14 days [1]. M8891 (iv; 0.2 mg/kg) has a small to moderate volume of distribution (Vss ~0.23-1.3 L/kg), moderate to high oral bioavailability (F ~40-80%), and low clearance (CL ~0.03-0.4 L/h/kg, or ~1-6% of hepatic blood flow) [1]. |
| Animal Protocol |
Animal/Disease Models: 6-7 weeks old female CD-1 nude mice with human U87-MG glioblastoma [1] Doses: 20 mg/kg Route of Administration: Po; one time/day for 14 days Experimental Results: demonstrated Strong tumor growth inhibitory effect. Animal/Disease Models: Rats, dogs and monkeys [1] Doses: 0.2 mg/kg (pharmacokinetic/PK/PK analysis) Route of Administration: intravenous (iv) (iv)injection Experimental Results: demonstrated low clearance (CL ~0.03-0.4 L/h/kg corresponding to ~1-6% of hepatic blood flow), small to moderate volume of distribution (Vss ~0.23-1.3 L/kg), and moderate to high oral bioavailability (F ~40-80%). |
| References |
[1]. Identification of Methionine Aminopeptidase-2 (MetAP-2) Inhibitor M8891: A Clinical Compound for the Treatment of Cancer. J Med Chem. 2019 Dec 26;62(24):11119-11134. [2]. Abstract 3075: Antitumor activity of M8891, a potent and reversible inhibitor of methionine aminopeptidase 2. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~90 mg/mL (~233.55 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.40 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.40 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.08 mg/mL (5.40 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5950 mL | 12.9749 mL | 25.9498 mL | |
| 5 mM | 0.5190 mL | 2.5950 mL | 5.1900 mL | |
| 10 mM | 0.2595 mL | 1.2975 mL | 2.5950 mL |